title: The tachykinins substance P and hemokinin-1 favor the generation of human memory Th17 cells by inducing IL-1β, IL-23, and TNF-like 1A expression by monocytes.
abstract: The nervous system influences immune responses through the release of neural factors such as neuropeptides. Among them, the tachykinin substance P (SP) signals via the neurokinin 1 receptor (NK-1R), which is expressed by various immune cells. We thereby analyzed in this paper whether tachykinins may participate in human CD4(+) Th cell polarization. We report that SP and hemokinin-1 (HK-1) upregulate IL-17A and IFN-γ production by human memory CD4(+) T cells without affecting IL-4 and IL-10 production. SP and HK-1 switch non-Th17-committed CD4(+) memory T cells into bona fide Th17 cells and Th1/Th17 cells. In contrast, SP and HK-1 do not modulate the polarization of naive CD4(+) T cells. SP- and HK-1-induced Th17 cell generation is mediated through NK-1R and requires the presence of monocytes. SP and HK-1 trigger IL-1β, IL-6, and TNF-α production, upregulate IL-23 production, and enhance TNF-like 1A expression on monocyte surface. Neutralization experiments demonstrated that IL-1β, IL-23, and TNF-like 1A are involved in the SP- and HK-1-induced Th17 cell. The other members of the tachykinin family, neurokinins A and B, have no effect on the differentiation of naive and memory T cells. These results thereby show that SP and HK-1 are novel Th17 cell-inducing factors that may act locally on memory T cells to amplify inflammatory responses.
authors.affiliation: Centre de Recherche en Cancérologie Nantes-Angers, INSERM Unité 892, 49933 Angers, France.
authors.forename: Pierre
authors.initials: P
authors.lastname: Cunin
authors.forename: Antoine
authors.initials: A
authors.lastname: Caillon
authors.forename: Murielle
authors.initials: M
authors.lastname: Corvaisier
authors.forename: Erwan
authors.initials: E
authors.lastname: Garo
authors.forename: Mari
authors.initials: M
authors.lastname: Scotet
authors.forename: Simon
authors.initials: S
authors.lastname: Blanchard
authors.forename: Yves
authors.initials: Y
authors.lastname: Delneste
authors.forename: Pascale
authors.initials: P
authors.lastname: Jeannin
mesh_terms: D002450:Cell Communication / Q000235:genetics / Q000276:immunology; D002454:Cell Differentiation / Q000235:genetics / Q000276:immunology*; D016764:Cell Polarity / Q000235:genetics / Q000276:immunology; D002478:Cells, Cultured; D006801:Humans; D007156:Immunologic Memory / Q000235:genetics; D018836:Inflammation Mediators / Q000502:physiology; D053583:Interleukin-1beta / Q000096:biosynthesis* / Q000235:genetics / Q000502:physiology; D053759:Interleukin-23 / Q000096:biosynthesis* / Q000235:genetics / Q000502:physiology; D009000:Monocytes / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D013373:Substance P / Q000502:physiology*; D015320:Tachykinins / Q000502:physiology*; D058504:Th17 Cells / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D053380:Tumor Necrosis Factor Ligand Superfamily Member 15 / Q000096:biosynthesis* / Q000235:genetics / Q000502:physiology
chemical_list: D018836:Inflammation Mediators; D053583:Interleukin-1beta; D053759:Interleukin-23; C117026:TNFSF15 protein, human; D015320:Tachykinins; D053380:Tumor Necrosis Factor Ligand Superfamily Member 15; C507968:hemokinin-1; D013373:Substance P